The principal objective of this project is to study the mechanisms which bring about the symptoms of cerebral aging and presenile dementia. The research deals with one of the most important health problems in this country - - the mentally disabled aged patient. We expect to quantify the age-related neuronal loss in the central and peripheral nervous system in humans and animals. Studies will be carried out to determine whether pathological changes in the senile brains can be caused by an increase of antibrain antibodies. We will also study the pathogenesis of axonal and synaptic pathology in aged humans, animals, and experimental models. Experiments are proposed to determine the effect of chronic hypoxia and ischemiaas to neuronal and axonal loss. We also propose to continue the study of brain biopsies which come to us from this and other insititutions, and which are done in the course of diagnostic and therapeutic operative procedures. These are from cases with dementia, demyelinating disease, movement disorders, and metabolic disease. The methods of procedure outlined in this grant proposal include automated counting and measuring of glia and nerve cells by image analysis apparatus, light and electron microscopic studies, and biochemical and immunological methodology. Bibliographic references: Iqbal, Khalid; Wisniewski, Henryk M.; Grundke-Iqbal, Inge; Korthals, Jan K.; and Terry, Robert D.: Chemical Pathology of Neurofibrils. Neurofibrillary Tangles of Alzheimer's Presenile-Senile Dementia. Journal of Histochemistry and Cytochemistry; 23: 563 - 569, 1975. Terry, Robert D.; Fitzgerald, Carol A.; and farmer, Peter M.: Quantitative Neuropathology with Image Analysis Apparatus. Paper presented at meeting of the American Association of Neuropathologists, New York, June, 1975.